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Biomedical subjects

S Ozeki

Publications and source records attributed to S Ozeki.

At least 127 records · Page 7Linked to original sources

Disposition of fractionated 3H-heparin in rats.

To evaluate the disposition of fractionated 3H-heparin, high affinity fraction (fraction A) and low affinity fraction (fraction NA) to protamine were prepared in this study from commercial 3H-heparin by affinity chromatography on protamine-Sepharose and gel filtration chromatography. Following intravenous administration of fraction A to rats, it seemed that the radioactivity in plasma declined one-exponentially with time to a pseudo-steady-state level, and 20.5% of dose was excreted in urine in 5 h. However, following the administration of fraction NA to rats, the plasma radioactivity curve was different from that of fraction A, and 69.8% of dose was excreted in urine in 5 h. It was found that fraction A and fraction NA had the distinctly different disposition characteristics in the body. Additionally, whole-body autoradiography with fraction A showed that the liver, bone marrow, kidney cortex, salivary gland and intestine played an important role in the distribution of it. It was suggested by gel filtration chromatography and affinity chromatography that the main material of the radioactivity excreted in urine in 5 h has the same properties as that of the administered heparin fraction.

Animals↗

[Current status and future of brachytherapy].

This paper reviewed the development of brachytherapy for the past and at present. In Japan, remotely controlled high-dose-rate afterloading intracavitary treatment for uterine cervix carcinoma has become quite common and interstitial radiotherapy with 192Ir hairpin technique for intraoral carsinomas has also been in routine practice at an increased number of institutes in Japan. These has played a great role in eliminating the personnel exposure. Our present efforts are now directed to extend indications to some other cancers, such as bile-duct, pancreas, rectum and prostate. Nearly 20 patients with intraluminal insertion of 192Ir-wire and template technique with 192Ir-wire has just started to apply for rectal had prostate cancer. Permanent implant of 125I has been also of much interest.

Aged↗

Absorption, distribution and elimination of creatinine and urea in hyperthyroid mice.

The absorption, distribution and elimination of creatinine and urea, which are considered to pass through the water-filled pores of biological membranes easily, were investigated in hyperthyroid mice to clarify the effects of enhanced blood circulation rate on drug behaviour in the body. The elimination rate constant in hyperthyroid mice was significantly and considerably larger than that in the control in both creatinine and urea (p less than 0.01). This result might be based on the increased urinary excretion rate of these two chemicals in hyperthyroid mice. The result of autoradiographic study indicated that creatinine was distributed more homogeneously in hyperthyroid mice than the control at 30 s and 2 min following intravenous administration. It was probably caused by the enhanced membrane permeability to creatinine due to some physiological changes (e.g. blood flow rate and pressure) or to a change of membrane itself. The gastrointestinal absorption of these two chemicals were also evaluated by the expiratory excretion of 14CO2 following oral administration. The results suggested that creatinine might be absorbed more slowly in hyperthyroid mice than in the control, and that in the case of urea such a difference in absorption might not exist.

Animals↗

Disposition of tritium-labelled heparin in rats.

To evaluate the distribution of water soluble macromolecular compound in the body, heparin was selected as one of the model compounds. Urinary and fecal excretion, and plasma levels following intravenous administration of commercial 3H-heparin were investigated at three different dose levels. Whole-body autoradiography was also carried out periodically following intravenous administration of 3H-heparin at single dose level. The distribution of radioactivity following the administration of 3H-heparin was compared with that of 14C-polyethylene glycol 6000. The statistically significant but only very small differences in the pharmacokinetic parameters and in the urinary excretion were observed over the wide range of dose (0.20, 2.0 and 20 mg/kg). The decline of plasma radioactivity following the administration of 3H-heparin appeared to be biexponential with time and pharmacokinetic constants were calculated according to a two-compartment open model. Whole-body autoradiograms showed that the reticulo-endotherial system (R.E.S.) may play an important role in removal of the radioactivity of heparin from the circulating blood.

Animals↗

Distribution of creatinine following intravenous and oral administration to rats.

To evaluate the distribution of creatinine in rats, urinary, fecal and expiratory excretion, plasma levels and whole-body autoradiography following intravenous or oral administration of [carbonyl-14C]creatinine was investigated. More than 90% of the exogeneous creatinine was excreted in the urine in 24 hr following intravenous administration, and both fecal and expiratory excretion were only about 1%. In case of oral administration, however, it was found that expiratory excretion could not be neglected, ranging from about 1 to 30%. Plasma creatinine concentration-time curves following the intravenous administration (70.4 micrograms/kg or 400 mg/kg as creatinine) were analyzed according to a two-compartment open model. There were significant but very small differences in the pharmacokinetic parameters for these two doses. When these parameters were compared with those of urea, k12 and k21, which are transfer rate constants between compartment 1 and 2, for creatinine were significantly smaller than those of urea. On the other hand, k10 was larger in creatinine. Furthermore, (V'd)extrap for creatinine was about three times that of urea. Whole-body autoradiograms at 5 minutes following intravenous administration showed that exogeneous creatinine distributes with higher concentrations in liver, lung and kidney than in muscle and fat. This results was remarkably different from that of urea which distributes almost uniformly throughout the body at the same time. This difference observed in the autoradiograms would be the consequence of the fact that urea has larger k12 and k21 than creatinine.

Administration, Oral↗

Excretion of indomethacin into saliva following intravenous administration to dogs.

Parotid saliva (Pr) and mandibular-sublingual saliva (MS) were collected separately by means of permanent fistulae in order to investigate the excretion of indomethacin in saliva of dogs receiving a single intravenous dose of 20 mg/kg. Drops of citric acid solution were placed on the tongue to stimulate salivary secretion. The concentrations of indomethacin both in saliva and plasma declined biexponentially with time. There was a good linear relationship between the drug concentration in each saliva and plasma. The Pr and MS levels were 7.4% and 4.4% of the plasma levels, respectively. Indomethacin concentrations in Pr were significantly higher than in MS (p less than 0.05). The roles of salivary pH and salivary protein binding were discussed in respect to the mechanism of salivary excretion of the drug.

Animals↗

Disposition of creatinine and urea in bilaterally nephrectomized rats.

Bilaterally nephrectomized rats were used to investigate the disposition of creatinine when renal function is acutely decreased. The percentage of radioactivity recovered in the expired air in 11 hours following intravenous administration of [carbonyl-14C] creatinine immediately and 24 hours after nephrectomy was 0.54 and 3.24% respectively, and these values were significantly different (p less than 0.05). As it was considered that expiratory excretion is one of the major elimination routes in nephrectomized rats, mechanism of expiratory excretion was investigated by incubating [carbonyl-14C] creatinine with the intestinal contents of the rats chronically loaded with creatinine [carbonyl-14C] Creatinine was completely metabolized in that intestinal contents, but 14CO2 was not produced. When the mixture of the metabolites was administered orally or intravenously to chronically creatinine loaded rats, however, about 50% of the total radioactivity was excreted into the expired air in 5 hours. Furthermore, biliary excretion of the radioactivity following intravenous administration of [carbonyl-14] creatinine in the nephrectomized rats was much greater than that in normal rats. These results indicate that expiratory excretion following intravenous administration [carbonyl-14C] creatinine to nephrectomized rats would arise following intestinal absorption of the creatinine metabolites, which seem to be produced by intestinal microflora after biliary excretion of creatinine. The change of disposition for urea by bilaterally nephrectomy was also studied to compare with that for creatinine.

Administration, Oral↗

Protein binding effects of salivary excretion of phenobarbital in dogs.

The salivary excretion of phenobarbital was investigated by collecting parotid saliva (Pr) and mandibular-sublingual saliva (MS) separately after intravenous administration in beagle dogs. (1) The alterations in the proportions of saliva secreted by the different glands were produced by salivation stimulants such as citric acid, ascorbic acid, sodium chloride and sodium glutamate. (2) The phenobarbital concentrations in both Pr amd MS were lower than those in plasma. The drug concentrations in MS were significantly lower than in Pr with stimulus of 10% citric acid of 15% sodium chloride (p less than 0.05). There was a significant correlation between phenobarbital concentration in each saliva and plasma specimen ( p less than 0.05). (3) The stimulation with 10% citric acid produced higher saliva /plasma drug concentration ratios (S/P ratios: 0.923 +/- 0.175 for Pr, 0.633 +/- 0.073 for MS) than that with 15% sodium chloride (S/P ratios: 0.597 +/- 0.071 for Pr, 0.509 +/- 0.067 or MS). (4) The S/P ratios were hardly influenced by salivary flow rates, at least under the experimental conditions examined in this study. (5) The increased S/P ratios were observed with higher salivary pH and then the equation of Matin et al. 3) seemed to hold for the average values of salivary pH and S/P ratio. (6) The stimulation with 10% citric acid produced higher protein concentration in saliva and higher S/P ratio than that with 15% sodium chloride following alternate stimulations in the same dog.

Animals↗

Size and shape of charged micelles of ionic surfactants in aqueous salt solutions.

Light-scattering has been measured on aqueous NaCl solutions of dodecyldimethylammonium chloride and sodium dodecyl sulfate. From molecular weight determination it is confirmed that spherical micelles are formed at low NaCl concentrations, but at high NaCl concentrations the small micelles formed at the critical micelle concentration further associate to form large rod-like micelles with increasing micelle concentration. The reduction of repulsion between charged groups induces the sphere-rod transition of micelle shape. The dependence of molecular weight on ionic strength can be expressed by double logarithmic relations, which are dependent on the micelle shape. While dodecyldimethylammonium chloride dissolves even in 4.00 M NaCl, sodium dodecyl sulfate solutions exhibit some XXX in angular dissymmetry at NaCl concentrations higher than 0.50 M at low temperatures.

Journal Article↗